Chorea, Myoclonus & Tics
Hyperkinetic movement disorders are characterized by excessive, involuntary movements. Three of the most commonly encountered phenomenologies — chorea, myoclonus, and tics — each have distinct clinical features that guide differential diagnosis and treatment. This article reviews the identification, etiologic workup, and management of these disorders, drawing primarily from the Continuum Movement Disorders issue (August 2025).
Bottom Line
- Chorea: Random, purposeless, flowing movements; most common genetic cause in adults is Huntington disease; acute chorea workup should include glucose (nonketotic hyperglycemia), autoimmune panel, and brain MRI
- Myoclonus: Brief, shock-like jerks (positive) or sudden loss of muscle tone (negative); classify by distribution, timing, and etiology to guide treatment; valproate, levetiracetam, and clonazepam are first-line for cortical myoclonus
- Tics: Semivoluntary, suppressible movements with premonitory urge; CBIT is first-line treatment; only 3 FDA-approved medications (haloperidol, pimozide, aripiprazole); ecopipam is a promising new D1 antagonist
- VMAT2 inhibitors: Tetrabenazine, deutetrabenazine, and valbenazine are FDA-approved for chorea in HD and tardive dyskinesia
- Functional ticlike behavior (FTLB): Explosive onset at age ≥12, often linked to social media exposure during COVID-19 pandemic; treat with CBT, not antitic medications
Part 1: Chorea
Identification
Chorea describes involuntary movements that are random, purposeless, and unpredictable — brief and abrupt, free-flowing from one body part to another. Key examination features:
- Motor impersistence: Inability to sustain posture (tongue protrusion for 10 seconds; “milkmaid’s grip” with fluctuating handgrip intensity)
- Parakinesia: Choreiform movements blended into purposeful movements (e.g., adjusting eyeglasses to mask an arm movement)
- “Hung up” or pendular reflexes
- Ballism: High-amplitude chorea involving proximal joints (flinging limb movements)
- Athetosis: Continuous writhing movements of distal extremities (“piano-playing fingers”), often co-occurring with chorea
Examine patients without shoes and socks, with legs and feet suspended. Small-amplitude chorea is often best seen in the forehead and fingers.
Diagnostic Approach by Body Distribution
| Distribution | Potential Causes |
|---|---|
| Orobuccolingual | Tardive dyskinesia, chorea-acanthocytosis, McLeod syndrome, Lesch-Nyhan, Wilson disease, neuroferritinopathy, NMDA receptor encephalitis |
| Forehead | Huntington disease (not pathognomonic but helps distinguish from TD) |
| Hemibody | With lesion: vascular insult, nonketotic hyperglycemia, infection, tuberous sclerosis. Without lesion: Sydenham chorea, polycythemia vera |
Diagnostic Approach by Acuity
| Acuity | Typical Causes | Key Workup |
|---|---|---|
| Acute / Subacute | Structural (stroke), drug-induced, infectious, autoimmune/paraneoplastic, metabolic/endocrine, nonketotic hyperglycemia | Serum glucose, CBC with smear, CMP, thyroid, ESR, ANA, antiphospholipid antibodies, lupus anticoagulant, paraneoplastic panel, brain MRI, pregnancy test |
| Subacute (children) | Sydenham chorea (most common acute chorea in children); post-streptococcal | ASO titer, anti-DNase B, throat culture; can recur with OCP use or pregnancy (chorea gravidarum) |
| Chronic / Progressive | Genetic etiologies: Huntington disease, HD phenocopies, neuroacanthocytosis, Wilson disease, benign hereditary chorea, NBIA | Brain MRI + CT (calcifications), genetic testing, ceruloplasmin (<50 years), acanthocyte smear, whole exome/genome if targeted testing negative |
Huntington Disease
The most common inherited cause of chorea. Autosomal dominant; CAG trinucleotide repeat expansion on HTT gene (chromosome 4). US prevalence: ~5/100,000.
| CAG Repeats | Clinical Significance |
|---|---|
| <26 | Normal |
| 27–35 (intermediate) | Normal (rare cases); risk of anticipation in offspring |
| 36–39 (indeterminate) | Incomplete penetrance; later onset |
| ≥40 | Full penetrance; mean onset age 30–50 |
| ≥60 | Juvenile onset; parkinsonism and seizures (Westphal variant) |
Clinical triad: chorea + cognitive decline + neuropsychiatric symptoms. Psychiatric features (depression, irritability, impulsivity, psychosis) frequently precede motor onset. Suicidal ideation prevalence up to 30%; suicide is the third most common cause of death (6.6%). MRI shows caudate atrophy (“boxcar ventricles”).
HD Phenocopies (HTT-negative)
- C9orf72 disease: Most common HD phenocopy in White populations; hexanucleotide repeat; may have upper motor neuron signs/weakness; also causes FTD and ALS
- SCA17 (HD-like 4): Second most common; CAG repeat in TBP gene; overlap of chorea and ataxia
- HD-like 2: CTG/CAG repeat in JPH3; exclusively in sub-Saharan African descent
- DRPLA: CAG repeat in ATN1; Japanese descent; seizures and myoclonus
Other Genetic Causes of Chorea
| Disorder | Inheritance | Key Features | Diagnostic Clues |
|---|---|---|---|
| Neuroferritinopathy | AD; FTL gene | Prominent orofacial dystonia | Very low serum ferritin; MRI T2 hypointensity in basal ganglia |
| Aceruloplasminemia | AR; CP gene | Retinal degeneration | Absent ceruloplasmin, high ferritin; MRI iron accumulation |
| Chorea-acanthocytosis | AR; VPS13A | Feeding dystonia, tongue protrusion, seizures, neuropathy | Acanthocytes, elevated CK, absent chorein in RBCs |
| McLeod syndrome | X-linked; XK gene | Similar to chorea-acanthocytosis; males only | Reduced Kell antigen, acanthocytes, elevated CK/LFTs |
| Benign hereditary chorea | AD; NKX2-1 | Brain-lung-thyroid syndrome; childhood onset, minimal progression | Congenital hypothyroidism, pulmonary disease; cancer screening |
| Wilson disease | AR; ATP7B | Treatable; variable movement disorders + liver disease | Low ceruloplasmin, elevated 24h urine Cu, KF rings, “face of giant panda” on MRI |
Pharmacologic Management of Chorea
| Agent | Mechanism | FDA Approved For | Key Considerations |
|---|---|---|---|
| Tetrabenazine | VMAT2 inhibitor | HD chorea (2008) | 3x daily dosing; CYP2D6 metabolism; boxed warning for suicidality; parkinsonism, akathisia, depression |
| Deutetrabenazine | VMAT2 inhibitor (deuterated) | HD chorea; TD | Longer half-life, 2x daily; better tolerability than tetrabenazine; less depression risk |
| Valbenazine | VMAT2 inhibitor | TD; HD chorea (2023) | Once daily; newest approval for HD chorea |
| Antipsychotics | Postsynaptic D2 blockade | Off-label for chorea | Useful when psychiatric comorbidities coexist; risk of TD with long-term use; lower-cost option globally |
Initial treatment for secondary chorea should always target the underlying cause. Mild chorea may not require pharmacologic treatment. Anosognosia may limit patient awareness, so care partners should be involved in treatment decisions.
Part 2: Myoclonus
Definition and Classification
Myoclonus is a fast, jerking movement with either gain of muscle tone (positive myoclonus) or sudden loss of muscle tone (negative myoclonus/asterixis). Unlike chorea, myoclonus lacks the flowing quality from one body part to another. Classification guides treatment:
| Classification Axis | Categories |
|---|---|
| By distribution | Focal, segmental, multifocal, generalized |
| By timing | Spontaneous, action-induced, stimulus-sensitive (reflex), intention |
| By neuroanatomic origin | Cortical (most common treatable form), subcortical, brainstem (reticular reflex myoclonus), spinal, peripheral |
| By etiology | Physiologic (hiccups, sleep starts), essential, epileptic, symptomatic (secondary) |
Key Etiologies
| Category | Examples |
|---|---|
| Physiologic | Hiccups, sleep starts (hypnic jerks), exercise-induced, anxiety-related |
| Essential | Essential myoclonus (often hereditary, responds to alcohol); myoclonus-dystonia (SGCE mutations, AD) |
| Epileptic | Juvenile myoclonic epilepsy, progressive myoclonic epilepsies (Unverricht-Lundborg, Lafora body, neuronal ceroid lipofuscinosis), infantile spasms |
| Post-hypoxic | Lance-Adams syndrome (chronic post-hypoxic action myoclonus after cardiac arrest) |
| Metabolic | Uremia, hepatic failure (asterixis), hyponatremia, hypoglycemia, hypercalcemia |
| Toxic / Drug-induced | Opioids, SSRIs, lithium, bismuth, levodopa, anticonvulsants |
| Neurodegenerative | CJD (stimulus-sensitive), CBD (cortical reflex), DLB, MSA, AD, HD |
| Autoimmune | Opsoclonus-myoclonus syndrome (neuroblastoma in children, usually seronegative; anti-Ri/ANNA-2 with breast or small-cell lung cancer in adults), stiff-person spectrum, NMDA receptor encephalitis |
| Spinal | Propriospinal myoclonus (axial jerks, worse supine); segmental spinal myoclonus (myelopathy, syrinx) |
Evaluation
- EEG with back-averaging: Cortical myoclonus shows a time-locked cortical potential preceding the jerk
- Somatosensory evoked potentials (SSEPs): Giant SEPs suggest cortical myoclonus
- EMG: Burst duration <75 ms suggests cortical origin; >200 ms suggests subcortical
- MRI brain and spine (if spinal myoclonus suspected)
- Metabolic workup: Renal/hepatic function, electrolytes, drug levels
Treatment of Myoclonus
| Myoclonus Type | First-Line Treatment | Alternatives |
|---|---|---|
| Cortical myoclonus | Valproate, levetiracetam, clonazepam | Piracetam (not available in US), perampanel, zonisamide |
| Subcortical / Reticular | Clonazepam | Valproate, levetiracetam |
| Post-hypoxic (Lance-Adams) | Levetiracetam + clonazepam combination | Valproate, piracetam; sodium oxybate in severe cases |
| Myoclonus-dystonia (SGCE) | Alcohol (diagnostic clue); zonisamide, benzodiazepines | DBS (GPi) for refractory cases |
| Spinal myoclonus | Clonazepam | Treat underlying cause (myelopathy, tumor) |
| Metabolic (asterixis) | Correct the underlying metabolic derangement | — |
Part 3: Tics and Tourette Syndrome
Epidemiology
- Tourette syndrome global prevalence: 0.5% (0.77% in children, 0.05% in adults)
- More common in boys (1.5:1 to 4:1 ratio); no racial/ethnic differences
- Onset typically ages 4–7; peak severity ages 8–12; significant improvement or resolution in early adulthood
- >85% of patients with Tourette syndrome have at least one psychiatric comorbidity (OCD 30–50%, ADHD 50–60%)
Clinical Features
| Feature | Description |
|---|---|
| Simple motor tics | Blinking, nose twitching, neck snapping, tensing muscles |
| Complex motor tics | Copropraxia (rude gestures), echopraxia (mimicking), hitting, throwing |
| Simple phonic tics | Sniffing, throat clearing, grunting, squeaking |
| Complex phonic tics | Coprolalia (10–30%), echolalia, palilalia |
| Premonitory urge | 82% report urge before tic; 57% find urge more bothersome than the tic itself |
| Suppressibility | Hallmark feature distinguishing tics from other hyperkinetic movements; urge builds during suppression |
| Waxing and waning | Tics fluctuate; new tics emerge, old tics fade; worsened by stress/sleep deprivation |
Diagnosis
DSM-5 criteria for Tourette syndrome: ≥2 motor tics + ≥1 phonic tic, present for ≥1 year, onset before age 18. If only motor or only phonic: chronic motor/vocal tic disorder. If <1 year: provisional tic disorder.
Functional Ticlike Behavior (FTLB)
A significant increase in explosive acute-onset ticlike behavior occurred during the COVID-19 pandemic, often linked to social media exposure (“#tourette” viewed >5 billion times on TikTok). Diagnostic criteria (European Society for the Study of Tourette Syndrome, 2022):
- Major criteria (all 3 required for “definite”): Age of onset ≥12 years; rapid symptom progression; ≥4 of 9 phenomenologic features
- Key distinguishing features from Tourette: Onset in trunk/extremities (not face), complex tics at onset, 87% female (vs. 76% male in TS), associated with depression/anxiety rather than OCD/ADHD, no response to antitic medications, responsive to CBT
Treatment of Tics
Treatment Algorithm
- Psychoeducation: All patients — explain natural history, waxing/waning course, expected improvement in adulthood; watchful waiting acceptable if tics are not functionally impairing
- Treat comorbidities: OCD (CBT first-line > SSRIs), ADHD (stimulants do NOT worsen tics overall; guanfacine/clonidine help both), depression/anxiety
- Behavioral intervention (CBIT): First-line treatment; 8 sessions over 10 weeks; combines habit reversal therapy + exposure/response prevention + psychoeducation; reduces tics 26–31% (similar to medications); benefits persist in 74% at 1 year
- Pharmacotherapy: When CBIT unavailable/insufficient or tics are severe
- Botulinum toxin: For focal tics, especially with strong premonitory urge
- Neuromodulation/DBS: Pallidal or thalamic DBS for medication-refractory, severe tics
Pharmacologic Options for Tics
| Class | Agents | Evidence Level | Key Notes |
|---|---|---|---|
| α2-Adrenergic agonists | Clonidine, guanfacine | Moderate / Low | First-line medication class; best tolerated; also help ADHD; monitor for bradycardia, hypotension; taper to avoid rebound HTN |
| Atypical antipsychotics | Aripiprazole (FDA-approved ages 6–17), risperidone, ziprasidone | Moderate | Aripiprazole has safest CV/metabolic profile; risperidone useful for comorbid aggression; monitor weight, metabolic syndrome, EPS |
| Typical antipsychotics | Haloperidol (FDA; age ≥3), pimozide (FDA; age ≥12), fluphenazine | Moderate / Low | Effective but more EPS and TD risk; pimozide requires ECG and CYP2D6 genotyping; reserve for refractory cases |
| GABAergic agents | Topiramate, clonazepam, baclofen, levetiracetam | Low / Very Low | Topiramate: avoid weight gain; baclofen: consider for dystonic tics; clonazepam: comorbid anxiety only, addiction risk |
| VMAT2 inhibitors | Deutetrabenazine, valbenazine, tetrabenazine | Failed primary endpoints | Clinical trials failed primary tic reduction endpoint but reported improved QoL; consider as add-on for refractory cases |
| Selective D1 antagonist | Ecopipam | D1AMOND trial positive | First-in-class; phase 3 D1AMOND withdrawal trial met its primary endpoint (reduced relapse risk) with tic (YGTSS) improvement in the open-label phase; well-tolerated (headache, somnolence, insomnia); promising new option |
| Botulinum toxin | OnabotulinumtoxinA | Moderate | Focal tics (face, neck); targeting the area of the premonitory urge most beneficial |
Distinguishing Hyperkinetic Movements
| Feature | Chorea | Myoclonus | Tics |
|---|---|---|---|
| Quality | Random, flowing, dance-like | Sudden, shock-like jerk | Patterned, stereotyped |
| Speed | Brief but slower than myoclonus | Lightning-fast (<100 ms) | Variable; can be brief or sustained |
| Pattern | Unpredictable, non-stereotyped | Variable; may be patterned in epileptic forms | Stereotyped, repetitive |
| Suppressibility | Partially suppressible | Not suppressible | Suppressed for variable periods (hallmark) |
| Premonitory urge | No | No | Yes (82%) |
| Worsening with action | May worsen | Action myoclonus prominent | Worsens with stress, not typically with action |
References
- Continuum (Minneap Minn). August 2025; 31(4 Movement Disorders). Articles: Huntington Disease and Chorea (pp 1066–1087); Tourette Syndrome and Tic Disorders (pp 1120–1137).
- Caviness JN. Treatment of myoclonus. Neurotherapeutics. 2014;11(1):188–200.
- Zutt R, van Egmond ME, Elting JW, et al. A novel diagnostic approach to patients with myoclonus. Nat Rev Neurol. 2015;11(12):687–697.